Immunoassay for the in vitro determination of OC 125 reactive determinants. These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer, excluding those with cancer of low malignant potential. The Elecsys® CA 125II is indicated for use as an aid in the detection of residual or recurrent ovarian carcinoma in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures. The Elecsys CA 125II assay is further indicated for serial measurement of CA 125II to aid in the management of cancer patients.

Device Description

The Elecsys® CA 125 II™ employs a sandwich test principle with monoclonal antibodies directed against CA 125 II and with streptavidin microparticles and electrochemiluminescence detection. Total duration of assay: 18 minutes.

1st Incubation: 40 ul of sample, a biotinylated monoclonal CA 125 IIspecific antibody and a monoclonal CA 125 II-specific antibody labeled with a ruthenium complex react to form a sandwich complex.
2nd Incubation: after the addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin.
The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier.
Results are determined via a calibration curve which is instrumentspecifically generated by 2-point calibration and a master curve provided via the reagent bar code.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the Boehringer Mannheim Corporation Elecsys® CA 125II on Elecsys® 1010, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The submission primarily focuses on demonstrating substantial equivalence of the Elecsys® CA 125II assay on the Elecsys 1010 to the same assay on the predicate device, Elecsys 2010. Therefore, the "acceptance criteria" are implicitly a demonstration of comparable performance to the predicate device. The table below outlines the performance characteristics presented for both systems. Specific predefined acceptance ranges or thresholds (e.g., "%CV must be less than X%") are not explicitly stated in the provided text as "acceptance criteria" but rather are presented as the device's performance achieved in the study.

Feature	Acceptance Criteria (Implicitly, comparable to Elecsys 2010)	Elecsys 1010 Reported Performance	Elecsys 2010 Reported Performance (Predicate)
Precision
Within-Run %CV	Low values, comparable to predicate	0.76 - 1.15% (Controls/Pools)	1.41 - 3.29% (Controls/Pools)
		0.84 - 0.76% (Pools)	2.14 - 2.06% (HS med/high)
Total %CV	Low values, comparable to predicate	2.13 - 3.13% (Controls/Pools)	2.48 - 4.19% (Controls/Pools)
		2.82 - 2.13% (Pools)	3.05 - 2.48% (HS med/high)
Lower Detection Limit	Comparable to predicate	0.222 U/mL	0.5 U/mL
Linearity	0.6 - 5,000 U/ml	0.6 - 5,000 U/ml	0.6 - 5,000 U/ml
Method Comparison	High correlation (r value close to 1) and slopes/intercepts indicative of agreement	Vs Elecsys 2010:Least Squares: y=0.9614x - 2.15, r=0.997Passing Bablock: y=0.9745x + 3.15, r=0.997	Vs CENTOCOR CA 125 II RIA:Least Squares: y=0.93x + 5.57, r=0.98Passing/Bablock: y=0.98x + 5.08, r=0.98
Hook Effect	No Hook Effect (up to a specified concentration)	No Hook Effect up to 24,000 U/ml CA 125	No Hook Effect up to 30,000 U/mL CA 125

2. Sample Size Used for the Test Set and Data Provenance

Precision: For each of the "Control" and "Pool" samples tested across both Elecsys 1010 and Elecsys 2010, the sample size (N) was 60. It is not explicitly stated if these were prospective or retrospective samples, or their country of origin.
Method Comparison (Elecsys 1010 vs Elecsys 2010): N = 93 samples.
Method Comparison (Elecsys 2010 vs CENTOCOR CA 125 II RIA): N = 139 samples.

The data provenance (e.g., country of origin, retrospective/prospective nature) is not specified in the provided text.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

This submission is for an in-vitro diagnostic (IVD) assay that measures a biomarker (CA 125II) in serum/plasma. As such, the "ground truth" for the test set is established by the reference measurement method (in this case, other CA 125II assays or a defined concentration of the analyte), not by expert human interpretation of images or clinical findings. Therefore, information regarding "number of experts" and their "qualifications" is not applicable in the context of this type of device and study.

4. Adjudication Method for the Test Set

Not applicable for this type of IVD device and study. The accuracy of measurements is determined by comparison to reference methods or known concentrations, not by adjudication of human interpretations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. An MRMC study is relevant for devices where human reader performance is a critical component, often in interpretation of medical images. This submission is for an automated immunoassay, and thus, an MRMC study was not performed.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies presented are for the standalone performance of the Elecsys® CA 125II assay on both the Elecsys 1010 and Elecsys 2010 automated immunoassay analyzers. There is no human-in-the-loop component for the measurement process itself.

7. The Type of Ground Truth Used

The "ground truth" for this IVD device is based on different levels:

Precision: The ground truth is the inherent variability of the assay when measuring known control or pooled samples.
Linearity: The ground truth is the expected linear relationship between the measured value and a series of diluted samples with known concentrations.
Method Comparison: The ground truth is established by the results from a predicate device (Elecsys 2010) or another commercially available comparative assay (CENTOCOR CA 125 II RIA). This implies that these predicate/comparative assays are themselves accepted reference methods for CA 125II measurement.

8. The Sample Size for the Training Set

The provided text describes studies for performance characteristics (precision, linearity, method comparison, hook effect) which are typically part of a verification and validation phase for an IVD, demonstrating the device meets its design specifications. It does not explicitly mention a "training set" for an algorithm in the sense of machine learning. If the term "training set" refers to the samples used to establish a calibration curve or reagent stability, that information is not detailed in this summary beyond the mention of "2-point calibration and a master curve provided via the reagent bar code." The focus is on the performance of the assay itself once calibrated.

9. How the Ground Truth for the Training Set Was Established

As noted above, a distinct "training set" with ground truth in the context of a machine learning algorithm is not detailed here. For the calibration mentioned ("2-point calibration and a master curve"), the ground truth would be established using reference materials or calibrators with accurately known concentrations of CA 125II, according to standard laboratory practices and manufacturers' protocols. The specific process for establishing these reference values is not provided in this summary.

Summary

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K980240

Boehringer Mannheim Corporation Elecsys® CA 125II on Elecsys® 1010 510(k) January, 1998

MAR 25 1998

510(k) Summary

Elecsys® CA 125II on Elecsys 1010

Introduction According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

1. Submitter name, address, contact	Boehringer Mannheim Corporation 4300 Hacienda Drive P.O. Box 9002 Pleasanton, CA 94566-0900 (510) 730-8415 Contact Person: Jody J. Savage Date Prepared: January 22, 1998
2. Device name	Proprietary name: Elecsys® CA 125 II ™ Common name: Epithelial Ovarian Tumor Associated Antigen Classification name: Tumor Associated Antigen Immunological Test System

We claim substantial equivalence to the Elecsys® CA 125IITM Assay on Predicate device Elecsys 2010.

CA125 1010 510(k).doc

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510(k) Summary, Continued

The Elecsys® CA 125 II™ employs a sandwich test principle with Device monoclonal antibodies directed against CA 125 II and with streptavidin Description microparticles and electrochemiluminescence detection.

Total duration of assay: 18 minutes.

· 1st Incubation: 40 ul of sample, a biotinylated monoclonal CA 125 IIspecific antibody and a monoclonal CA 125 II-specific antibody labeled with a ruthenium complex react to form a sandwich complex.
2nd Incubation: after the addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin.

·The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier.

·Results are determined via a calibration curve which is instrumentspecifically generated by 2-point calibration and a master curve provided via the reagent bar code.

Immunoassay for the in vitro determination of OC 125 reactive determinants. 5. Intended use These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer, excluding those with cancer of low malignant potential. The Elecsys® CA 125II is indicated for use as an aid in the detection of residual or recurrent ovarian carcinoma in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures. The Elecsys CA 125II assay is further indicated for serial measurement of CA 125II to aid in the management of cancer patients.

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510(k) Summary, Continued

The Boehringer Mannheim Elecsys® CA 125II Assay is under review for use on the Elecsys 2010 immunoassay analyzer (K972162). The application of the Comparison to Elecsys® CA 125II Assay on the Elecsys 1010 immunoassay analyzer is predicate device substantially equivalent to the same assay (Elecsys CA 125II Assay) on the Elecsys 2010. The following table compares the Elecsys® CA 125II on the Elecsys 1010 with the predicate device, Elecsys® CA 125II on the Elecsys 2010. Specific data on the performance of this test for both the Elecsys 1010 and 2010 have been incorporated into the draft labeling in Section 5. Labeling for the predicate device provided in Section 6 will be replaced upon the approval of this premarket approval submission with the combined Elecsys 2010 and 1010 insert (Section 5).

Similarities:

·Intended Use: Immunoassay for the in vitro determination of OC 125 reactive determinants. These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer, excluding those with cancer of low malignant potential. The Elecsys® CA 125II is indicated for use as an aid in the detection of residual or recurrent ovarian carcinoma in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures. An assay value of greater than or equal to 35 U/ml is predictive of residual disease. The Elecsys CA 125II assay is further indicated for serial measurement of CA 125II to aid in the management of cancer patients.

· Assay range: 0.6 - 5000 U/mL

· Assay methodology: Sandwich immunoassay

·Kit (cat. no. 1776223) intended for use on the Elecsys 2010 (K972162)

·Sample and reagent volumes

·Incubation temperature and reaction times

·Package insert

·Performance specifications

·Reagents

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510(k) Summary, Continued

Differences:

Comparison to predicate device cont.

Feature	Elecsys 1010	Elecsys 2010
Instrumentrequired	Elecsys 1010	Elecsys 2010
InstrumentSystem	Batch	Random access
ReagentStorage Temp(C)	Ambient Temperature	20° C

Performance Characteristics:

Feature	Elecsys 1010			Elecsys 2010
Precision	Modified NCCLS (U/mL):			Modified NCCLS (U/mL):
Sample	Control 1	Control 2	Pool 1	TM1	TM 2	HS low
N	60	60	60	60	60	60
Within-Run	41.8	129.2	44.1	39.03	121.45	7.83
%CV	0.98	1.15	1.15	1.91	1.41	3.29
Total	41.8	129.2	44.1	39.03	121.45	7.83
%CV	2.26	2.65	3.13	2.53	2.70	4.19
	Modified NCCLS (ng/mL):			Modified NCCLS (U/mL):
	Pool 2	Pool 3		HS med	HS high
N	60	60		60	60
Within-Run	142.9	591.4		38.28	70.82
%CV	0.84	0.76		2.14	2.06
Total	142.9	591.4		38.28	70.82
%CV	2.82	2.13		3.05	2.48

Continued on next page

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ﺟ

510(k) Summary, Continued

Performance Characteristics:

predicate device, cont.

Comparison to

Feature	Elecsys 1010	Elecsys 2010
LowerDetection Limit	0.222 U/mL	0.5 U/ml
Linearity	0.6 - 5,000 U/ml	0.6 - 5,000 U/ml
MethodComparison	Vs Elecsys 2010	vs. CENTOCOR CA 125 IIRIA
	Least Squares:$y=0.9614x - 2.15$$r=0.997$$SEE=47.22$$N=93$	Least Squares:$N = 139$$y = 0.93x + 5.57$$r = 0.98$
	Passing Bablock$y=0.9745x + 3.15$$r=0.997$$SEE=16.76$$N=93$	Passing/Bablock$N = 139$$y = 0.98x + 5.08$$r = 0.98$
Hook Effect	No Hook Effect up to24,000 U/ml CA 125	No Hook Effect up to30,000 U/mL CA 125

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/11 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an abstract symbol resembling a stylized eagle or bird in flight, composed of three curved lines.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Patricia M. Klimley Manager, Requlatory Affairs Boehringer Mannheim Corporation Laboratory Diagnostics 4300 Hacienda Drive P.O. Box 9002 Pleasanton, California 94566-0900

MAR 2 5 1998

Re : K980240 Trade Name: Elecsys® CA 125 II™ Requlatory Class: II Product Code: LTK Dated: January 22, 1998 Received: January 23, 1998

Dear Ms. Klimley:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major requlations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Reqister. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Requlations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 510 (k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): N/A

Device Name: Elecsys® CA 125Assay

Indications For Use:

Immunoassay for the in vitro determination of OC 125 reactive determinants. These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer, excluding those with cancer of low malignant potential. The Elecsys® CA 125II is indicated for use as an aid in the detection of residual or recurrent ovarian carcinoma in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures. The Elecsys CA 125II is further indicated for serial measurement of CA 125II to aid in the management of cancer patients.

Deborah M. Moore
for D. Peter Mafim
(Division Sign Off)

Division Sian-Off Division of Clinical Labora 510(x) Number

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use OR Over-The-Counter Use __ (Per 21 CFR 801.109)

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.